AI Article Synopsis
- Certain BH3-only proteins bind to and activate Bak and Bax, leading to the breakdown of the mitochondrial outer membrane, which is crucial for apoptosis.
- The first crystal structures of an activator BH3 peptide binding to Bak have been described, providing insights into the activation process.
- Engineered BH3 derivatives have been created to inhibit Bak activation on mitochondria by competing for the same binding site, highlighting important conformational changes during Bak activation.
Article Abstract
Certain BH3-only proteins transiently bind and activate Bak and Bax, initiating their oligomerization and the permeabilization of the mitochondrial outer membrane, a pivotal step in the mitochondrial pathway to apoptosis. Here we describe the first crystal structures of an activator BH3 peptide bound to Bak and illustrate their use in the design of BH3 derivatives capable of inhibiting human Bak on mitochondria. These BH3 derivatives compete for the activation site at the canonical groove, are the first engineered inhibitors of Bak activation, and support the role of key conformational transitions associated with Bak activation.
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| http://dx.doi.org/10.1016/j.molcel.2017.11.001 | DOI Listing |
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